Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics... | NCT01230801

ID	Type	Description	Link
2010-023561-22	EudraCT Number

Label	Type	Description	Intervention Names
BMN 701	Experimental	IV infusion	Biological: BMN 701

Name	Type	Description	Arm Group Labels	Other Names
BMN 701	Biological	GILT-tagged recombinant human GAA	BMN 701

Measure	Description	Time Frame
Number of Participants With Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	24 weeks

Measure	Description	Time Frame
Change From Baseline in Six Minutes Walk Test	Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes	Baseline up to 24 weeks

Measure	Description	Time Frame
Change From Baseline in Percent Predicted Upright Forced Vital Capacity	Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.	Baseline up to 24 week
Change From Baseline in Percent Predicted Supine Forced Vital Capacity

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Patient has been diagnosed with Pompe Disease prior to or during the screening period based on 2 GAA gene mutations and either: endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed in cultured skin fibroblasts -or- endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed by dried blood spot or whole blood assay;
Patient is male or female and 13 years of age or older at the time of enrollment in the study;
Sexually active patients must be willing to use an acceptable method of contraception while participating in the study and for at least 4 months following the last dose of BMN 701;
If patient is female and not considered to be of childbearing potential, she is at least 2 years post-menopausal or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy;
If patient is female and of childbearing potential, she has negative urine pregnancy tests during the Screening Period and at the Baseline visit and be willing to have additional pregnancy tests during the study;
Patient has ≥30% predicted upright FVC and either <80% predicted upright FVC, or >10% reduction in supine FVC compared to upright FVC during the Screening Period;
Patient is naïve to Enzyme Replacement Therapy (ERT) with rhGAA;
Patient must be able to ambulate at least 40 meters (131.2 feet) on the 6MWT conducted at the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted); and
If subject was female, she was not lactating

Exclusion criteria:

Patient has a history of diabetes or other disease known to cause hypoglycemia and is currently receiving, or might anticipate receiving, hypoglycemic agents during the course of the study;
Patient has been on any immunosuppressive medication other than glucocorticosteroids within 1 year prior to enrollment into this study;
Patient requires invasive ventilatory assistance at the time of enrollment into the study;
Patient has received any investigational medication within 30 days prior to the first dose of study drug or is scheduled to receive any investigational drug other than BMN 701 during the course of the study;
Patient has previously been admitted to the study;
Patient is breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study;
Patient has a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the patient's ability to comply with the protocol requirements or compromise the patient's well being or safety;
Patient has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Name	Affiliation	Role
Medical Monitor	BioMarin Pharmaceutical	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Univ of California San Diego School of Medicine		La Jolla	California	92103-8765	United States
University of Florida College of Medicine

ID	Title	Description
FG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
FG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV

ID	Title	Description
BG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
BG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
BG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0013 BG00216 BG00322

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Events

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Safety Population

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV

Units	Counts
Participants	OG0003 OG0013 OG00216

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0013 OG00215

Secondary

Change From Baseline in Six Minutes Walk Test

Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes

ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point.

Posted

Mean

Standard Deviation

meter

Baseline up to 24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total Results

Other Pre-specified

Change From Baseline in Percent Predicted Upright Forced Vital Capacity

Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Posted

Mean

Standard Deviation

percentage of Predicted Upright FVC

Baseline up to 24 week

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total Results

Other Pre-specified

Change From Baseline in Percent Predicted Supine Forced Vital Capacity

Change from Baseline in Percent Predicted Supine Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Posted

Mean

Standard Deviation

percentage of Predicted Supine FVC

Baseline up to 24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total Results

Other Pre-specified

Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure

Change from Baseline in Percent Predicted Upright Maximum Expiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Posted

Mean

Standard Deviation

percentage of Predicted MEP

Baseline up to 24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total IV

Other Pre-specified

Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure

Change from Baseline in Percent Predicted Upright Maximum Inspiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Posted

Mean

Standard Deviation

percentage of Predicted MIP

Baseline up to 24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total Results

Other Pre-specified

Change From Baseline in Upright Maximum Ventilatory Volume

Change from Baseline in Upright Maximum Ventilatory Volume. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.

Posted

Mean

Standard Deviation

L/min

Baseline up to 24 weeks

ID	Title	Description
OG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV
OG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV
OG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV
OG003	Total	Total Results

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG0031 events1 affected22 at risk
Bundle branch block right	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Palpitations	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0024 events3 affected16 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG00216 events4 affected16 at risk EG003
Diplopia	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Vision blurred	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected16 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0025 events4 affected16 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG00215 events8 affected16 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Retching	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected16 at risk EG003
Tongue discolouration	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0029 events5 affected16 at risk EG003
Application site erythema	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Asthenia	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Chest discomfort	General disorders	MedDRA 16.1	Systematic Assessment	EG0006 events1 affected3 at risk EG0012 events1 affected3 at risk EG0026 events5 affected16 at risk EG003
Chills	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0023 events3 affected16 at risk EG003
Fatigue	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Feeling cold	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected16 at risk EG003
Feeling hot	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events3 affected16 at risk EG003
Infusion site discomfort	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Local swelling	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected16 at risk EG003
Malaise	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events2 affected16 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Oedema peripheral	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events3 affected16 at risk EG003
Pain	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected16 at risk EG003
Pyrexia	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Tenderness	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Thirst	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Vaccination site inflammation	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Vessel puncture site bruise	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Candida infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Laryngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Localised infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0023 events2 affected16 at risk EG003
Sinusitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Animal bite	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0024 events3 affected16 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0015 events3 affected3 at risk EG0024 events3 affected16 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Blood glucose decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Body temperature increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Cardiac murmur	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Complement factor decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Respiratory rate increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events1 affected16 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Hyperphagia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG00241 events14 affected16 at risk EG003
Lactic acidosis	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected16 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0004 events2 affected3 at risk EG0010 events0 affected3 at risk EG0023 events2 affected16 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0024 events3 affected16 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Dizziness	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0029 events6 affected16 at risk EG003
Headache	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0018 events2 affected3 at risk EG00227 events6 affected16 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected16 at risk EG003
Lethargy	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Tremor	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0024 events3 affected16 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Depression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Depressive symptom	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Nervousness	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0022 events2 affected16 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG00210 events5 affected16 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Hypopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0023 events3 affected16 at risk EG003
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected16 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected16 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0024 events2 affected16 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events4 affected16 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0024 events1 affected16 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG00213 events1 affected16 at risk EG003
Flushing	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0005 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Haematoma	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Hot flush	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Hypertension	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events3 affected16 at risk EG003
Hypotension	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Pallor	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected16 at risk EG003
Poor venous access	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected16 at risk EG003
Systolic hypertension	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Venous thrombosis	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003

ID	Term
D020140	Lysosomal Storage Diseases, Nervous System
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D006008	Glycogen Storage Disease
D002239	Carbohydrate Metabolism, Inborn Errors
D016464	Lysosomal Storage Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BMN 701 5 mg/kg	BMN 701 5 mg/kg IV	3	0	3	3	3
EG001	BMN 701 10 mg/kg	BMN 701 10 mg/kg IV	3	0	3	3	3
EG002	BMN 701 20 mg/kg	BMN 701 20 mg/kg IV	16	4	16	15	16
EG003	Total	Total Results	22	4	22	21	22

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypersensitivity	Immune system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG0031 events1 affected22 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Aggression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected16 at risk EG003